托特罗定缓释片治疗膀胱过度活动症的临床研究

目的评价酒石酸托特罗定缓释片治疗膀胱过度活动症的有效性与安全性。方法采用随机、双盲、双模拟平行对照的方法对膀胱过度活动症220例进行托特罗定缓释片剂型组（观察组,110例）和托特罗定原剂型组（对照组,110例）对比研究。托特罗定缓释片,每片4 mg,每日1次,口服;托特罗定片,每片2 mg,每日2次,口服。各连服6周。结果治疗后观察组24 h平均排尿次数由（12.21±3.10）次降至（8.50±2.31）次,24 h平均每次排尿量由（119.80±30.54）ml增至（215.50±68.52）ml、24 h平均尿失禁次数由（2.88±2.5）次减至（0.07±0.38）次。治疗前后比较,有极显著差异（P〈0.01）。两组治疗后相比较,无显著性差异。观察组对药物不良反应发生率为38.0%,中毒发生率为18.5%;对照组分别为40.8%和20.0%,总发生率两者无显著性差异（P〉0.05）。结论托特罗定缓释片与托特罗定片,其疗效与不良反应基本相同。但托特罗定缓释片,用药次数少,服用方便,为膀胱过度活动症治疗药物的最佳选择。     

酒石酸托特罗定与奥昔布宁双盲双模拟随机对照治疗膀胱过度活动症多中心临床研究

目的评价国产酒石酸托特罗定治疗膀胱过度活动症的有效性和安全性.方法以盐酸奥昔布宁为对照,采用随机双盲双模拟多中心临床试验设计,对237例(托特罗定组114例,奥昔布宁组123例)膀胱过度活动症患者进行研究,服药方法每日2次,每次托特罗定2mg或奥昔布宁5mg.结果治疗6周后,试验组(n=109)和对照组(n=108)24h平均排尿次数减少、尿失禁患者的平均尿失禁次数减少以及平均每次尿量增加比较无统计学差异(P＞0.05).试验组患者不良事件的总发生率48.2%,其中主要不良事件口干发生率为32.5%;而奥昔布宁组不良事件的总发生率为65.0%,口干发生率为55.3%,不良事件总发生率及口干发生率在两组间均有统计学差异(P＜0.05).结论托特罗定是治疗膀胱过度活动症的有效药物,其疗效与奥昔布宁等效,但其药物不良反应明显低于奥昔布宁.     

国产酒石酸托特罗定片治疗膀胱过度活动症的临床研究

目的 :研究国产酒石酸托特罗定片治疗膀胱过度活动症的疗效和安全性。方法 :选择膀胱过度活动症56例 ,随机分为托特罗定组和奥昔布宁组各28例 ,疗程6周。结果 :托特罗定片和奥昔布宁片治疗膀胱过度活动症疗效相当 ,前者的不良反应发生率低于后者。结论 :托特罗定片是治疗膀胱过度活动症更为理想的药物     

托特罗定治疗前列腺术后膀胱过度活动症20例

目的:观察经尿道前列腺切除(TUP)术后早期使用托特罗定对早期膀胱过度活动症症状的临床疗效.方法:采用随机对照单盲临床试验设计,将38例术后患者随机分为两组.试验组(20例)于手术当日起即口服托特罗定,2 mg/次,至拔除尿管后3 d停药.结果:试验组膀胱痉挛每日发作次数、持续时间、术后膀胱持续冲洗引流液转清时间、拔除尿管时间、每日排尿次数及急迫性尿失禁发作次数均低于对照组(P均＜0.01),而平均每次排尿量高于对照组(P＜0.01).试验组口干的发生率高于对照组(P＜0.01),消化不良和便秘发生率与对组照无显著差异(P＞0.05).结论:托特罗定对于预防和治疗TUP术后早期膀胱痉挛临床疗效确切,能明显改善拔管早期尿频和急迫性尿失禁症状.     

托特罗定联合氟哌噻吨美利曲辛治疗膀胱过度活动症临床观察

目的 探讨托特罗定联合氟哌噻吨美利曲辛治疗女性膀胱过度活动症（OAB）的临床疗效及安全性.方法 选择确诊为女性膀胱过度活动症患者84例,采用随机数字表法分为观察组和对照组各42例.观察组42例采用托特罗定联合氟哌噻吨美利曲辛治疗,对照组42例单用托特罗定治疗,4周后记录并比较两组临床疗效.结果 观察组总有效率明显优于对照组（95.24％比76.19％,x2=6.291,P＜0.05）;两组平均24h排尿次数、平均24 h尿失禁次数、初始尿意容量及最大膀胱压容量差异均有统计学意义（均P＜0.05）.结论 托特罗定联合氟哌噻吨美利曲辛治疗女性膀胱过度活动症具有疗程短、疗效高、不良反应少等优点.     

前列腺电切术后膀胱过度活动症的药物疗效观察

目的 探讨前列腺电切术后膀胱过度活动症应用托特罗定药物治疗的疗效观察.方法 共入组病例64例.其中对照组为回顾性研究病例32例,术后给予应用硬膜外镇痛泵治疗.试验组32例,术后给予酒石酸托特罗定口服,2 mg,2次/d.观察疗效.结果 对照组有效率87.5%,治愈率81.25%,复发率15.625%;试验组有效率93.75%,治愈率90.625%,无复发病例.结论 酒石酸托特罗定治疗前列腺电切术后膀胱过度活动症疗效确切,方法简单,易于推广.     

托特罗定联合吲哚美辛栓治疗女性膀胱过度活动症疗效分析与评价

目的 探讨女性膀胱过度活动症的有效治疗方法.方法 选择诊断为膀胱过度活动症的患者118例,随机分为两组,治疗组60例给予托特罗定2mg,口服,2次/d,同时予吲哚美辛栓100mg,纳肛,2次/d;对照组58例仅服用相同剂量的托特罗定,用药时间为4周,观察24h平均排尿次数、24h平均尿失禁次数、24h平均单次尿量、24h单次最大尿量.结果 治疗组与对照组用药前后各指标比较差异有统计学意义(P＜0.05).结论 托特罗定联合吲哚美辛栓治疗女性膀胱过度活动症是一种效果显著而安全的方法.     

酒石酸托特罗定联合盐酸坦洛新治疗膀胱过度活动症的临床效果观察

目的：探讨酒石酸托特罗定联合盐酸坦洛新治疗膀胱过度活动症（OAB）的临床效果。方法选择诊断为OAB且口服酒石酸托特罗定胶囊后无效的30例患者,在口服酒石酸托特罗定胶囊的基础上加盐酸坦洛新缓释胶囊,0.2 mg,口服,1次/d,治疗4周,观察用药前后膀胱过度活动症症状评分（OABSS）的变化。结果治疗前后尿急评分、OABSS总分比较,差异有统计学意义（P〈0.05）。出现药物不良反应4例,主要表现为轻度抗胆碱能作用,其中口干、眼干2例,轻度便秘1例,消化不良1例,不良反应发生率为13.3%（4/30）,患者均能耐受,未因此而停止用药。结论酒石酸托特罗定联合盐酸坦洛新可有效改善单纯口服酒石酸托特罗定无效的OAB患者的临床症状,提高患者的生活质量。     

酒石酸托特罗定预防前列腺电切术后膀胱痉挛的疗效分析

目的探讨酒石酸托特罗定预防前列腺电切术后膀胱痉挛的临床疗效。方法将64例行经尿道前列腺电切术(TURP)的患者术后随机分为治疗组(酒石酸托特罗定片组)和对照组(双氯芬酸钠栓组)各32例,术后72h注意观察膀胱痉挛发生次数、膀胱痉挛平均持续时间及膀胱冲洗转清时间。结果治疗组发生膀胱痉挛次数、膀胱痉挛持续时间及膀胱冲洗转清时间均少于对照组。结论 TURP术后早期预防性使用托特罗定片是有效解决膀胱痉挛的方法,能减少并发症的发生。     

补肾通淋汤治疗女性膀胱过度活动症96例的临床观察

目的探讨补肾通淋汤治疗膀胱过度活动症（OAB）的疗效。方法 OAB女性患者96例,随机分为治疗组48例和对照组48例。治疗组应用补肾通淋汤100ml,2次/d口服,对照组应用酒石酸托特罗定片2mg,日2次口服）,两组疗程均为4周。分别于治疗前、后以患者生活质量评分（BS）、排尿记录（平均每次尿量、24h平均排尿次数）、国际LUTS症状程度轻、中、重评分和最大尿流率为疗效评判标准评价两组疗效。结果治疗4周后,治疗组总有效率为91.67%,对照组总有效率83.33%,治疗组治疗女性特异性膀胱过度活动症与对照组疗效相当;治疗组患者不良事件的总发生率为0%。对照组不良事件总发生率为36.5%。治疗后国际LUTS评分以及最大尿流率比较,治疗组均明显优于对照组（P〈0.05）。两组治疗前后生活质量评分（BS）、平均每次排尿量以及24h排尿次数均比治疗前有明显改善（P〈0.05）,但治疗组与对照组治疗后疗效对比差异无统计学意义（P〉0.05）。结论补肾通淋汤是治疗膀胱过度活动症安全、有效的方药。     

Benefit-risk assessment of tolterodine in the treatment of overactive bladder in adults.

Overactive bladder is associated with symptoms of urgency, with or without urge incontinence, usually with daytime frequency and nocturia in the absence of local pathological factors. Muscarinic receptor antagonists (antimuscarinics) are the first-line pharmacotherapy. Tolterodine, a competitive, nonselective antimuscarinic specifically developed for the treatment of overactive bladder, demonstrated tissue selectivity for the bladder over the parotid gland in an animal model. As of March 5, 2003, the immediate-release (IR) formulation had been approved in 72 countries and the extended-release (ER) formulation had been approved in 28 countries, and tolterodine had been administered to 5 million patients. This review evaluates the benefit-risk profile of tolterodine in the treatment of adults with overactive bladder, summarising clinical trial and postmarketing surveillance data.Tolterodine has been found to significantly reduce micturition frequency, urgency perception and the number of episodes of urge incontinence and increase the volume voided per micturition. Dry mouth, an antimuscarinic class effect, is the most commonly reported adverse effect but is mostly mild to moderate in severity. Serious adverse effects are reported infrequently. Based on summary and review of postmarketing surveillance and clinical trial safety data received by the market authorization holder and contained in the Periodic Safety Update Reports for tolterodine, several monitored serious events of the gastrointestinal tract (e.g. ileus or haemorrhage), nervous system (e.g. syncope, convulsions and memory disorders) and cardiovascular system (e.g. ventricular arrhythmia, atrial fibrillation, palpitations, bradycardia, transient ischaemic attacks and hypertension) were not considered related to tolterodine. QT or corrected QT (QTc) prolongation was not observed in any of the five cases of verified ventricular arrhythmia in patients administered tolterodine; there is insufficient evidence to indicate that tolterodine causes ventricular arrhythmia or extrasystoles or any specific type of cardiac rhythm abnormality. The safety profile of tolterodine is similar in patients aged > or =65 years and in younger adults. Clinically relevant drug interactions are limited to cytochrome P450 3A4 inhibitors, such as ketoconazole, and co-administration with such agents warrants a tolterodine dosage decrease.In addition, tolterodine IR 2mg twice daily is similar in efficacy to oxybutynin IR 5mg three times daily, and tolterodine ER 4 mg once daily is similar in efficacy to oxybutynin ER 10mg once daily. Dry mouth occurred less frequently with tolterodine than oxybutynin, and moderate to severe dry mouth occurred more than three times less frequently. Based on the low frequency of adverse events, the absence of unexpected adverse events and the very low frequency of serious adverse events, we conclude that tolterodine is a well tolerated treatment for overactive bladder in adults, in whom it should be considered as first-line therapy.     

Multiple dose pharmacokinetics of a new once daily extended release tolterodine formulation versus immediate release tolterodine

OBJECTIVE: To determine the multiple dose pharmacokinetics of a new extended release (ER) capsule formulation of tolterodine, compared with the existing immediate release (IR) tablet, in healthy volunteers. DESIGN: Nonblind, randomised, 2-way crossover trial. PARTICIPANTS: 19 healthy volunteers (7 females, 12 males), mean age 33 years (range 18 to 55 years). Prior to the study, all volunteers were classified as either extensive or poor metabolisers by cytochrome P450 2D6 genotyping. METHODS: Volunteers received tolterodine ER 4mg once daily or tolterodine IR 2mg twice daily for 6 days (all doses given as the L-tartrate salt). A washout period of 7 days separated the 2 treatments. Serum concentrations of tolterodine, its active 5-hydroxymethyl metabolite (5-HM) and the active moiety (extensive metabolisers: sum of unbound tolterodine + 5-HM; poor metabolisers: unbound tolterodine) were measured for up to 48 hours post-dose on day 6 (steady state). Tolerability was also determined. RESULTS: 17 volunteers (13 extensive metabolisers, 4 poor metabolisers) completed the study and were evaluable for both treatment periods. The 90% confidence interval for the geometric mean ratio of area under the serum concentration-time curve to 24 hours (AUC24) of the active moiety, for all volunteers combined, indicated equivalence for the 2 formulations. Pooled analysis also demonstrated that the peak serum concentration (Cmax) of the active moiety following administration of tolterodine ER was around 75% of that observed for the IR tablet, whereas the trough concentration was around 1.5-fold higher. Overall, the pharmacokinetics of tolterodine (irrespective of genotype) and 5-HM (extensive metabolisers only) were consistent with sustained drug release over 24 hours. Tolterodine ER was well tolerated. CONCLUSIONS: The new once daily ER formulation of tolterodine 4mg shows pharmacokinetic equivalence (AUC24) to the existing IR tablet given at a dose of 2mg twice daily. Findings of lower Cmax for tolterodine ER may explain the significantly lower rate of dry mouth subsequently observed in patients with overactive bladder.     

Tolterodine: a review of its use in the treatment of overactive bladder

Tolterodine is a competitive muscarinic receptor antagonist that shows in vivo selectivity for the bladder over the salivary glands compared with oxybutinin. Results of randomised double-blind placebo-controlled studies indicate that tolterodine 4 mg/day (administered as immediate-release tablets 2mg twice daily or extended-release capsules 4mg daily) is superior to placebo in improving micturition diary variables in patients with overactive bladder. Moreover, tolterodine 2mg twice daily is as effective as oxybutynin 5mg 3 times daily. Maximum treatment effects with both drugs occurred after 5 to 8 weeks of treatment and improvements were maintained during long term treatment for up to 24 months. In a pooled analysis of four 12-week studies, equivalent and significant reductions in micturition frequency (-2.3 and -2.0 vs -1.4, p < 0.001) and the incidence of urge incontinence episodes (-1.6 and -1.8 vs -1.1, p < 0.05) were reported for tolterodine 2mg twice daily and oxybutynin 5mg 3 times daily compared with placebo. Functional bladder capacity was also significantly increased. Improvements in patient perceptions of their urgency symptoms and of problems caused by their bladder condition were significantly greater during treatment with tolterodine than with placebo. Tolterodine was generally well tolerated in clinical trials of up to 24 months' duration. Dry mouth was the most frequent adverse event. The incidence (40 vs 78%, p < 0.001) and intensity of this event was lower with tolterodine 2mg twice daily than oxybutynin 5mg 3 times daily. Additionally, a 23% lower incidence of dry mouth was reported with once daily extended-release tolterodine capsules than with twice daily immediate-release tablets (p < 0.02). The incidence of adverse CNS events with tolterodine was low and similar to that of placebo. Tolterodine was well tolerated in elderly patients and no serious tolerability concerns were identified. CONCLUSION: Tolterodine is the first antimuscarinic agent to specifically developed for the treatment of overactive bladder. The functional selectivity of tolterodine for the bladder translates into good efficacy and tolerability in patients, including the elderly, with overactive bladder. Tolterodine is as effective as oxybutynin in improving micturition diary variables but is associated with a significantly lower incidence and intensity of dry mouth. This favourable tolerability profile, together with sustained clinical efficacy during long term treatment, places tolterodine as valuable treatment for the symptoms of overactive bladder.     

Food does not influence the pharmacokinetics of a new extended release formulation of tolterodine for once daily treatment of patients with overactive bladder

OBJECTIVE: To determine whether food intake influences the pharmacokinetics of a new, once daily, extended release (ER) capsule formulation of tolterodine in healthy volunteers, and to compare its bioavailability with that of the existing immediate release (IR) tablet. DESIGN: Open, randomised, 3-way crossover trial. PARTICIPANTS: 17 healthy volunteers (3 females, 14 males) aged between 19 and 50 years. With the exception of 1 male volunteer, all participants were classified as extensive metabolisers by cytochrome P450 2D6 genotyping. METHODS: Volunteers received single oral doses of tolterodine L-tartrate ER 8 mg (2 x 4 mg capsules) on an empty stomach or with a standardised high-fat breakfast. Reference therapy comprised tolterodine L-tartrate IR 4 mg (2 x 2 mg tablets), administered in the fasting state. Serum concentrations of tolterodine, its active 5-hydroxymethyl metabolite (5-HM) and the active moiety (sum of unbound tolterodine + 5-HM) were measured for up to 72 hours post-dose. Safety endpoints were also determined. RESULTS: No effect of food on the bioavailability of tolterodine ER capsules was apparent and there was no sign of dose-dumping with meals. The geometric mean fed:fasting ratio of area under the serum concentration-time curve to infinity (AUCinfinity) of the active moiety, for all volunteers combined, was 0.95 (90% confidence interval 0.88 to 1.03). Equivalence with respect to AUCinfinity (dose-corrected) was also found for the ER capsule compared with the IR tablet, although uncorrected maximum serum concentrations were around 50% lower despite the fact that the capsule dose was twice as high. Seven volunteers reported adverse events, predominantly headache. No volunteer reported dry mouth. Overall, there were no safety concerns. CONCLUSIONS: The new ER formulation of tolterodine shows no pharmacokinetic interaction with food. On the basis of these results, patients with overactive bladder may, therefore, be advised to take the drug without regard to the timing of meals, maximising convenience during therapy.     

Solifenacin in overactive bladder syndrome

Solifenacin is a bladder-selective, muscarinic (M(1) and M(3)) receptor antagonist. In animal studies, the selectivity of solifenacin for the bladder over the salivary glands was greater than that of tolterodine, oxybutynin, darifenacin or atropine. In large, 12-week, randomised, double-blind, multicentre clinical trials, solifenacin 5 and 10mg once daily improved symptoms of overactive bladder syndrome (OAB) [urinary urgency, frequency, incontinence and nocturia] and increased functional bladder capacity to a significantly greater extent than placebo. Solifenacin 5 or 10mg once daily was noninferior to tolterodine extended release (ER) 4mg daily for improving urinary frequency and had significantly greater efficacy than tolterodine ER for improving other symptoms of OAB (episodes of urgency, incontinence and urge incontinence) and increasing functional bladder capacity. At least half of all patients receiving solifenacin who were incontinent at baseline were continent by study end in the three comparative studies reporting this parameter. Health-related quality of life was significantly improved with once-daily solifenacin 5 or 10mg versus placebo, as assessed in two 12-week double-blind studies; the improvement was maintained during a 40-week extension study. Solifenacin was generally well tolerated; the most frequently reported adverse events were dry mouth, constipation and blurred vision.     

Oxybutynin extended-release: a review of its use in the management of overactive bladder

The OROS-based oxybutynin extended-release (ER) formulation (Lyrinel XL; Ditropan XL) represents a new form of oral delivery for oxybutynin, a muscarinic receptor antagonist used in the treatment of overactive bladder (OAB). The release of oxybutynin from oxybutynin ER occurs in a sustained manner, resulting in a smoother plasma concentration-time profile and a lower maximum plasma concentration than those seen with oxybutynin immediate-release (IR). The ER formulation has been developed with the aim of improving the tolerability of oxybutynin therapy and facilitating once-daily administration. Moreover, oxybutynin ER offers greater flexibility in dosage (5-30 mg/day) than the other available treatment options. At dosages of 5-30 mg once daily, oxybutynin ER produced significant decreases from baseline in weekly urinary urge incontinence in patients with OAB. In addition, there were significant decreases in weekly total incontinence episodes and micturition frequency. In two randomised, double-blind studies in patients with OAB, the improvement in all the symptoms with once-daily oxybutynin ER 5-30 mg/day was similar to that produced by oxybutynin IR 5-20 mg/day given one to four times daily. Once-daily oxybutynin ER 10 mg was superior to tolterodine IR 4 mg/day given as two daily doses and as effective as once-daily tolterodine ER 4 mg/day in decreasing urinary incontinence; the decreases in micturition frequency with oxybutynin ER were significantly greater than those seen with either of tolterodine formulations. Oxybutynin ER was well tolerated in all the trials, with adverse events usually being mild to moderate and transient. In direct comparisons, the overall tolerability profile of oxybutynin ER was better than that of oxybutynin IR. Oxybutynin ER was similar to tolterodine (IR and ER) with respect to the incidence of clinically important dry mouth. A large 12-month tolerability study demonstrated no significant risks associated with the long-term use of oxybutynin ER. A few noncomparative studies have shown promising results with oxybutynin ER in the treatment of adult and paediatric patients with neurogenic bladder dysfunction secondary to neuronal injury. Long- and short-term studies have reported significant improvements in health-related quality of life with oxybutynin ER therapy. In addition, pharmacoeconomic studies have suggested that oxybutynin ER is more cost effective than oxybutynin IR and at least as cost effective as tolterodine IR. In conclusion, oxybutynin ER shows excellent efficacy in the treatment of symptoms associated with OAB in adults and the elderly with a good tolerability profile over a prolonged period of use (12 months). The ER formulation of oxybutynin provides a smooth plasma concentration profile over the 24-hour dosage interval, facilitating once-daily administration. Hence, given its overall efficacy/tolerability profile and dosage flexibility, oxybutynin ER provides an excellent treatment option in the first-line pharmacotherapy of OAB.     

托特罗定治疗顽固性膀胱痉挛34例

目的 观察托特罗定治疗顽固性频繁发作膀胱痉挛的临床疗效和安全性。方法 采用随机、双盲的方法对68例膀胱痉挛频繁发作病人进行托特罗定与异搏停的对比研究,服药方法每日2次,每次托特罗定2mg或异搏停80mg。观察两组显效例数、起效时间、维持时间及不良反应。结果 托特罗定组34例中显效33例(97.1％),异搏停组34例中显效28例(82.4％)。起效时间两组差异无显著意义(P>0.05),但维持时间托特罗定组长于异搏停组,差异有显著性意义(P<0.01)。托特罗定组病人副作用发生率29％,而异搏停组发生率为87.1％,两组间差别有显著意义(P<0.01)。结论 托特罗定是治疗顽固性频繁发作膀胱痉挛的有效药物,疗效好于异搏停,且不良反应明显低于异搏停。